A Case Report of Germline Compound Heterozygous Mutations in the BRCA1 Gene of an Ovarian and Breast Cancer Patient

The germline carrier of the BRCA1 pathogenic mutation has been well proven to confer an increased risk of breast and ovarian cancer. Despite BRCA1 biallelic pathogenic mutations being extremely rare, they have been reported to be embryonically lethal or to cause Fanconi anemia (FA). Here we describe a patient who was a 48-year-old female identified with biallelic pathogenic mutations of the BRCA1 gene, with no or very subtle FA-features. She was diagnosed with ovarian cancer and breast cancer at the ages of 43 and 44 and had a strong family history of breast and gynecological cancers.     

Calf massager: Intervention for body muscle discomfort during prolonged standing

Many occupations require workers to stand for long periods of time without proper interventions, which causes discomfort in the back and lower limbs. Therefore, this study aims to assess the effectiveness in alleviating body muscle discomfort during prolonged standing through the use of a calf massager. This study was conducted among male workers at a manufacturer with production line workers and the list was obtained from the HR Department and simple random sampling was done by number categorization. A total of 100 respondents (50 respondents for both the control and the experimental groups) participated in this study. The experiment took place in a room with a similar setup for the production line. Each respondent was requested to perform the simulated task for 2 hr. For the experimental group, the calf massager was turned on every 15 min. At every 15‐min interval after turning on the calf massager, respondents from both groups were required to evaluate their discomfort level on a Borg's scale CR‐10 questionnaire. The results showed that the level of body discomfort among respondents in the experimental group reduced (20–30%) compared with that of the control group. Multivariate analysis results revealed that the discomfort rating for the lower back, knees, thighs, calves, and feet was significantly lower (p < .05) among the experimental group compared with the control group. For lower body parts, the lower back region was statistically significant (p < .05) at the 90th, 105th, and 120th min; the thigh region was statistically significant (p < .05) at the 120th min; the knee region was statistically significant (p < .05) at the 105th and 120th min; the calf region was statistically significant (p < .05) at all minute intervals except the 15th and 45th min, while the feet region, was statistically significant at the 105th and 120th min. Therefore, this study indicates that calf massage treatment is capable of reducing body muscle discomfort during prolonged standing and highlights the significance of calf massage.     

Sensitization of MCF7 Cells with High Notch1 Activity by Cisplatin and Histone Deacetylase Inhibitors Applied Together

Histone deacetylase inhibitors (HDIs) are promising anti-cancer agents that inhibit proliferation of many types of cancer cells including breast carcinoma (BC) cells. In the present study, we investigated the influence of the Notch1 activity level on the pharmacological interaction between cisplatin (CDDP) and two HDIs, valproic acid (VPA) and suberoylanilide hydroxamic acid (SAHA, vorinostat), in luminal-like BC cells. The type of drug–drug interaction between CDDP and HDIs was determined by isobolographic analysis. MCF7 cells were genetically modified to express differential levels of Notch1 activity. The cytotoxic effect of SAHA or VPA was higher on cells with decreased Notch1 activity and lower for cells with increased Notch1 activity than native BC cells. The isobolographic analysis demonstrated that combinations of CDDP with SAHA or VPA at a fixed ratio of 1:1 exerted additive or additive with tendency toward synergism interactions. Therefore, treatment of CDDP with HDIs could be used to optimize a combined therapy based on CDDP against Notch1-altered luminal BC. In conclusion, the combined therapy of HDIs and CDDP may be a promising therapeutic tool in the treatment of luminal-type BC with altered Notch1 activity.     

GOLPH3 Regulates EGFR in T98G Glioblastoma Cells by Modulating Its Glycosylation and Ubiquitylation

Protein trafficking is altered when normal cells acquire a tumor phenotype. A key subcellular compartment in regulating protein trafficking is the Golgi apparatus, but its role in carcinogenesis is still not well defined. Golgi phosphoprotein 3 (GOLPH3), a peripheral membrane protein mostly localized at the trans-Golgi network, is overexpressed in several tumor types including glioblastoma multiforme (GBM), the most lethal primary brain tumor. Moreover, GOLPH3 is currently considered an oncoprotein, however its precise function in GBM is not fully understood. Here, we analyzed in T98G cells of GBM, which express high levels of epidermal growth factor receptor (EGFR), the effect of stable RNAi-mediated knockdown of GOLPH3. We found that silencing GOLPH3 caused a significant reduction in the proliferation of T98G cells and an unexpected increase in total EGFR levels, even at the cell surface, which was however less prone to ligand-induced autophosphorylation. Furthermore, silencing GOLPH3 decreased EGFR sialylation and fucosylation, which correlated with delayed ligand-induced EGFR downregulation and its accumulation at endo-lysosomal compartments. Finally, we found that EGF failed at promoting EGFR ubiquitylation when the levels of GOLPH3 were reduced. Altogether, our results show that GOLPH3 in T98G cells regulates the endocytic trafficking and activation of EGFR likely by affecting its extent of glycosylation and ubiquitylation.     

An assessment of the Spanish national hydrological plan

The paper is a comprehensive review of the Spanish National Hydrological Plan, which proposes to transfer water from the lower part of the Ebro River up to the Levante basins, around 912 km away. The National Hydrological Plan is a conventional, static plan, which focuses primarily on supply management. The plan is based on the explicit assumption that the world will change only incrementally during its entire economic life of 100-200 years. The analysis indicates that much of the increased water demands forecasted are unlikely to materialize due to increasing emphasis on demand management practices, major structural changes in the agricultural sector that will occur by 2020 and the requirements of the Water Directive of the European Union, which must be fulfilled by 2010. Even now, the cost per cubic metre of water delivered at the end of the transfer is nearly twice the cost of desalinated water. The National Hydrological Plan in its present form cannot be justified for economic, environmental and social reasons. In addition, the plan will not be necessary if demand management practices are implemented.     

Crosslinking reactions and swelling behavior of matrices based on N-acryloyl-TRIS(hydroxymethyl)aminomethane

Summary In this study, new hydrogels in rod shape were prepared from N-acryloyl-TRIS(hydroxymethyl)aminomethane (NAT) using ethylene glycol dimethacrylate (EGDMA) or N,N’methylenebisacrylamide (BIS) as crosslinking agent, dimethylformamide (DMF) as solvent and benzoyl peroxide (BPO) as initiator. In most cases, 2-hydroxyethyl methacrylate (HEMA), acrylamide (Aam) or acrylic acid (Aac) were used as co-monomers. The polymeric matrices obtained by free radical polymerization exhibited different properties by changing crosslinker, crosslinker concentration, co-monomer and initial NAT/co-monomer mole ratio. Besides, hydrogels from HEMA, Aam and Aac with BIS in absence of NAT were prepared under the same experimental reaction conditions in order to compare the properties of these products with those synthesized from NAT and the respective co-monomers. Some of the final products were selected to perform urea release assays, conducted through swelling-controlled release. Urea was chosen as “model” plant fertilizer agent.     

Design of a wideband microstrip antenna and the use of artificial neural networks in parameter calculation

This paper deals with the design of a multi-slot hole-coupled microstrip antenna on a substrate of 2 mm thickness that gives multi-frequency (wideband) characteristics. The Method of Moments (MoM)-based IE3D software was used to simulate the results for return loss, VSWR, the Smith chart, and the radiation patterns. A tunnel-based artificial neural network (ANN) was also developed to calculate the radiation patterns of the antenna. The radiation patterns were measured experimentally at 10.5 GHz and 12 GHz. The experimental results were in good agreement with the simulated results from IE3D and those of the artificial neural network. A new method of using a genetic algorithm (GA) in an artificial neural network is also discussed. This new method was used to calculate the resonant frequency of a single-shorting-post microstrip antenna. The resonant frequency calculated using the genetic-algorithm-coupled artificial neural network was compared with the analytical and experimental results. The results obtained were in very good agreement with the experimental results.     

Lithiasis of the prostatic loge

Lithiasis may develop in the prostate loge following prostate surgery. Calculus formation in the prostate can be ascribed basically to foreign bodies, residual adenomatous spheroids and clots or fragments of sphacelous mucosa in the presence of a stenotic area after surgery and/or infection. The diagnosis is based on the physical examination and particularly on the radiological findings. Treatment is by open surgery or endoscopic or extracorporeal lithotripsy.